![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 302, Issue 3, 1055-1061, September 2002
Novartis Pharma Research, Basel, Switzerland (J.W., S.R., J.R.G.),
and Metastases Research Laboratory (K.B., A.B., V.C.) and Tumor Biology
Laboratory, University of Liége Sart Tilman, Liège, Belgium
(L.D., J.M.F.)
Bisphosphonate drugs inhibit osteoclastic bone resorption and are
widely used to treat skeletal complications in patients with
tumor-induced osteolysis. We now show that zoledronic acid, a new
generation bisphosphonate with a heterocyclic imidazole substituent, is
also a potent inhibitor of angiogenesis. In vitro, zoledronic acid
inhibits proliferation of human endothelial cells stimulated with fetal
calf serum, basic fibroblast growth factor (bFGF), and vascular
endothelial growth factor (IC50 values 4.1, 4.2, and 6.9 µM, respectively), and modulates endothelial cell adhesion and
migration. In cultured aortic rings and in the chicken egg
chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. When administered systemically to mice, zoledronic acid
potently inhibits the angiogenesis induced by subcutaneous implants
impregnated with bFGF [ED50, 3 µg/kg (7.5 nmol/kg)
s.c.]. These findings indicate that zoledronic acid has marked
antiangiogenic properties that could augment its efficacy in the
treatment of malignant bone disease and extend its potential clinical
use to other diseases with an angiogenic component.
This article has been cited by other articles:
|
|
 |
|
  P. D. Ottewell, J. K. Woodward, D. V. Lefley, C. A. Evans, R. E. Coleman, and I. Holen Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone Mol. Cancer Ther., October 1, 2009; 8(10): 2821 - 2832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Aragon-Ching and W. L. Dahut Osteonecrosis of the Jaw and the Use of Antiangiogenic Agents: Just an Association? Oncologist, December 1, 2008; 13(12): 1314 - 1314. [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Ottewell, H. Monkkonen, M. Jones, D. V. Lefley, R. E. Coleman, and I. Holen Antitumor Effects of Doxorubicin Followed by Zoledronic Acid in a Mouse Model of Breast Cancer J Natl Cancer Inst, August 20, 2008; 100(16): 1167 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Estilo, C. H. Van Poznak, T. Wiliams, G. C. Bohle, P. T. Lwin, Q. Zhou, E. R. Riedel, D. L. Carlson, H. Schoder, A. Farooki, et al. Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate Therapy Oncologist, August 1, 2008; 13(8): 911 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Stathopoulos, C. Moschos, H. Loutrari, A. Kollintza, I. Psallidas, S. Karabela, S. Magkouta, Z. Zhou, S. A. Papiris, C. Roussos, et al. Zoledronic Acid Is Effective against Experimental Malignant Pleural Effusion Am. J. Respir. Crit. Care Med., July 1, 2008; 178(1): 50 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Kearns, S. Khosla, and P. J. Kostenuik Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease Endocr. Rev., April 1, 2008; 29(2): 155 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Grbic, R. Landesberg, S.-Q. Lin, P. Mesenbrink, I. R. Reid, P.-C. Leung, N. Casas, C. P. Recknor, Y. Hua, P. D. Delmas, et al. Incidence of Osteonecrosis of the Jaw in Women With Postmenopausal Osteoporosis in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial J Am Dent Assoc, January 1, 2008; 139(1): 32 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Scavelli, G. Di Pietro, T. Cirulli, M. Coluccia, A. Boccarelli, T. Giannini, G. Mangialardi, R. Bertieri, A. M. L. Coluccia, D. Ribatti, et al. Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma Mol. Cancer Ther., December 1, 2007; 6(12): 3256 - 3262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Santini, B. Vincenzi, and G. Tonini Zoledronic Acid and Angiogenesis Clin. Cancer Res., November 15, 2007; 13(22): 6850 - 6851. [Full Text] [PDF]
|
|
|
|
 |
|
 S.L. Ruggiero and S.J. Drew Osteonecrosis of the Jaws and Bisphosphonate Therapy Journal of Dental Research, November 1, 2007; 86(11): 1013 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.B. Kimmel Mechanism of Action, Pharmacokinetic and Pharmacodynamic Profile, and Clinical Applications of Nitrogen-containing Bisphosphonates Journal of Dental Research, November 1, 2007; 86(11): 1022 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.R. Dass, T.M.N. Tran, and P.F.M. Choong Angiogenesis Inhibitors and the Need for Anti-angiogenic Therapeutics Journal of Dental Research, October 1, 2007; 86(10): 927 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Santini, B. Vincenzi, S. Galluzzo, F. Battistoni, L. Rocci, O. Venditti, G. Schiavon, S. Angeletti, F. Uzzalli, M. Caraglia, et al. Repeated Intermittent Low-Dose Therapy with Zoledronic Acid Induces an Early, Sustained, and Long-Lasting Decrease of Peripheral Vascular Endothelial Growth Factor Levels in Cancer Patients Clin. Cancer Res., August 1, 2007; 13(15): 4482 - 4486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.M. Phal, R.W.T. Myall, L.A. Assael, and J.L. Weissman Imaging Findings of Bisphosphonate-Associated Osteonecrosis of the Jaws AJNR Am. J. Neuroradiol., June 1, 2007; 28(6): 1139 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Kumar, B. Pass, S. A. Guttenberg, J. Ludlow, R. W. Emery, D. A. Tyndall, and R. J. Padilla Bisphosphonate-related osteonecrosis of the jaws: A report of three cases demonstrating variability in outcomes and morbidity J Am Dent Assoc, May 1, 2007; 138(5): 602 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Favus Diabetes and the Risk of Osteonecrosis of the Jaw J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 817 - 818. [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Landis, M. Richter, I. Dojcinovic, and M. Hugentobler Osteonecrosis of the jaw after treatment with bisphosphonates: Is irreversible, so the focus must be on prevention BMJ, November 11, 2006; 333(7576): 982 - 983. [Full Text] [PDF]
|
|
|
|
|
|
H. S. Yeh and J. R. Berenson Treatment for myeloma bone disease. Clin. Cancer Res., October 15, 2006; 12(20): 6279s - 6284s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Vessella and E. Corey Targeting factors involved in bone remodeling as treatment strategies in prostate cancer bone metastasis. Clin. Cancer Res., October 15, 2006; 12(20): 6285s - 6290s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hirbe, E. A. Morgan, O. Uluckan, and K. Weilbaecher Skeletal complications of breast cancer therapies. Clin. Cancer Res., October 15, 2006; 12(20): 6309s - 6314s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Sanna, L Preda, R Bruschini, M Cossu Rocca, S Ferretti, L Adamoli, E Verri, L Franceschelli, A Goldhirsch, and F Nole Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer Ann. Onc., October 1, 2006; 17(10): 1512 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Boyde Jaw Bone Necrosis and Bisphosphonates: Microanatomical Questions IBMS BoneKEy, September 1, 2006; 3(9): 19 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.G. Paterson The Role of Bisphosphonates in Early Breast Cancer Oncologist, September 1, 2006; 11(suppl_1): 13 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Van den Wyngaert, M. T. Huizing, and J. B. Vermorken Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? Ann. Onc., August 1, 2006; 17(8): 1197 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Q. Lacy, A. Dispenzieri, M. A. Gertz, P. R. Greipp, K. L. Gollbach, S. R. Hayman, S. Kumar, J. A. Lust, S. V. Rajkumar, S. J. Russell, et al. Mayo Clinic Consensus Statement for the Use of Bisphosphonates in Multiple Myeloma Mayo Clin. Proc., August 1, 2006; 81(8): 1047 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-B. Woo, J. W. Hellstein, and J. R. Kalmar Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws Ann Intern Med, May 16, 2006; 144(10): 753 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Caraglia, D. Santini, M. Marra, B. Vincenzi, G. Tonini, and A. Budillon Emerging anti-cancer molecular mechanisms of aminobisphosphonates. Endocr. Relat. Cancer, March 1, 2006; 13(1): 7 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Badros, D. Weikel, A. Salama, O. Goloubeva, A. Schneider, A. Rapoport, R. Fenton, N. Gahres, E. Sausville, R. Ord, et al. Osteonecrosis of the Jaw in Multiple Myeloma Patients: Clinical Features and Risk Factors J. Clin. Oncol., February 20, 2006; 24(6): 945 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mystakidou, E. Katsouda, E. Parpa, E. Kouskouni, C. Chondros, M. L. Tsiatas, A. Galanos, and L. Vlahos A prospective randomized controlled clinical trial of zoledronic acid for bone metastases American Journal of Hospice and Palliative Medicine, January 1, 2006; 23(1): 41 - 50. [Abstract] [PDF]
|
|
|
|
|
|
A. Bamias, E. Kastritis, C. Bamia, L. A. Moulopoulos, I. Melakopoulos, G. Bozas, V. Koutsoukou, D. Gika, A. Anagnostopoulos, C. Papadimitriou, et al. Osteonecrosis of the Jaw in Cancer After Treatment With Bisphosphonates: Incidence and Risk Factors J. Clin. Oncol., December 1, 2005; 23(34): 8580 - 8587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. MIGLIORATI, J. CASIGLIA, J. EPSTEIN, P. L. JACOBSEN, M. A. SIEGEL, and S.-B. WOO Managing the care of patients with bisphosphonate-associated osteonecrosis: An American Academy of Oral Medicine position paper J Am Dent Assoc, December 1, 2005; 136(12): 1658 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. MELO and G. OBEID Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: Strategies for prevention and early recognition J Am Dent Assoc, December 1, 2005; 136(12): 1675 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G A Clines and T A Guise Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone Endocr. Relat. Cancer, September 1, 2005; 12(3): 549 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. N. Hortobagyi Progress in the Management of Bone Metastases: One Continent at a Time? J. Clin. Oncol., May 20, 2005; 23(15): 3299 - 3301. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hashimoto, K.-i. Morishige, K. Sawada, M. Tahara, R. Kawagishi, Y. Ikebuchi, M. Sakata, K. Tasaka, and Y. Murata Alendronate Inhibits Intraperitoneal Dissemination in In vivo Ovarian Cancer Model Cancer Res., January 15, 2005; 65(2): 540 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Green Bisphosphonates: Preclinical Review Oncologist, September 1, 2004; 9(suppl_4): 3 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hiraga, P. J. Williams, A. Ueda, D. Tamura, and T. Yoneda Zoledronic Acid Inhibits Visceral Metastases in the 4T1/luc Mouse Breast Cancer Model Clin. Cancer Res., July 1, 2004; 10(13): 4559 - 4567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Migliorati Bisphosphanates and Oral Cavity Avascular Bone Necrosis J. Clin. Oncol., November 15, 2003; 21(22): 4253 - 4254. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bezzi, M. Hasmim, G. Bieler, O. Dormond, and C. Ruegg Zoledronate Sensitizes Endothelial Cells to Tumor Necrosis Factor-induced Programmed Cell Death: EVIDENCE FOR THE SUPPRESSION OF SUSTAINED ACTIVATION OF FOCAL ADHESION KINASE AND PROTEIN KINASE B/Akt J. Biol. Chem., October 31, 2003; 278(44): 43603 - 43614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Santini, U. Vespasiani Gentilucci, B. Vincenzi, A. Picardi, F. Vasaturo, A. La Cesa, N. Onori, S. Scarpa, and G. Tonini The antineoplastic role of bisphosphonates: from basic research to clinical evidence Ann. Onc., October 1, 2003; 14(10): 1468 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H L Neville-Webbe and R E Coleman The use of zoledronic acid in the management of metastatic bone disease and hypercalcaemia Palliative Medicine, September 1, 2003; 17(6): 539 - 553. [Abstract] [PDF]
|
|
|
|
|
|
D. Santini, B. Vincenzi, G. Dicuonzo, G. Avvisati, C. Massacesi, F. Battistoni, M. Gavasci, L. Rocci, M. C. Tirindelli, V. Altomare, et al. Zoledronic Acid Induces Significant and Long-Lasting Modifications of Circulating Angiogenic Factors in Cancer Patients Clin. Cancer Res., August 1, 2003; 9(8): 2893 - 2897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wilhelm, V. Kunzmann, S. Eckstein, P. Reimer, F. Weissinger, T. Ruediger, and H.-P. Tony {gamma}{delta} T cells for immune therapy of patients with lymphoid malignancies Blood, July 1, 2003; 102(1): 200 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Vincenzi, D. Santini, L. Rocci, and G. Tonini Bisphosphonates: new antiangiogenic molecules in cancer treatment? Ann. Onc., May 1, 2003; 14(5): 806 - 807. [Full Text] [PDF]
|
|
|
|
|
|
P. Fournier, S. Boissier, S. Filleur, J. Guglielmi, F. Cabon, M. Colombel, and P. Clezardin Bisphosphonates Inhibit Angiogenesis in Vitro and Testosterone-stimulated Vascular Regrowth in the Ventral Prostate in Castrated Rats Cancer Res., November 15, 2002; 62(22): 6538 - 6544. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
